新生兒篩檢個案CBS基因缺陷研究-以戶籍台東個案為主

Abstract

背景:因為典型高胱胺酸尿症在台灣地區住民特定族群中有好發的突變點，而且其盛行率與經由新生兒篩檢的發生率相距甚大，因此現行新生兒篩檢方式的敏感性需要被重新檢視。 方法:本研究以基因分析搭配甲硫胺酸數值分析，檢驗台灣地區新生兒 1.p.D47E突變的帶因率; 2.台灣地區新生兒篩檢採用甲硫胺酸做為標誌物是否無法偵測p.D47E突變的典型高胱胺酸患者。 結果:新生兒篩檢血片抽取的DNA可以用allelic specific PCR的方式，找到適當的條件後，進行大量檢體的篩檢已知單點鹼基突變。實驗結果顯示，檢測3357個來自抽樣地區(台東)的新生兒，只有2人為帶有此突變的帶因者，帶因率為1/3357，預估的疾病發生率約低於百萬分之一。 結論與展望:本實驗的結果顯示，CBS基因p. D47E突變在台東地區的帶因率僅1/3,357；因此預測此種患者在全台地區的盛行率極低，目前新生兒篩檢仍不須加做基因突變分析或改用血片高胱胺酸濃度篩檢以減少偽陰性率。未來對於高胱胺酸尿症患者的篩檢策略是否需要調整，例如全面改以血片高胱胺酸濃度篩檢，基因篩檢或是針對特定族群使用不同的篩檢策略，將需要進一步研究分析，以提供公共衛生政策參考。

Background: A mutation of the CBS gene associated with classical homocystinuria been discovered in Taiwan. The high incidence of the gene however, is inconsistent with results of neonatal screening, indicating that the sensitivity of the current protocol (methionine levels detected by tandem mass spectrometry) should be reassessed. In this research, we proposed that tandem mass spectrometry coupled with the allelic-specific PCR could make an early recognition easier and more reliable. Methods: In this study, we determined the carrier rate of p.D47E mutation by allelic-specific PCR, by establishing relationship between the p.D47E mutation and levels of methionine detected through tandem mass spectrometry. Results: Genomic DNA from blood spots was proven suitable for allelic-specific PCR. Wide scale screening for p.D47E mutation was performed, and results showed that only 2 out of 3,357 newborns from the Taitung area were heterozygous carries. The carrier rate of p.D47E mutation was 1/3,357, making the estimated incidence of homocystinuria less than one in a million. The levels of homocysteine in these two heterozygous carriers has not increased. Conclusion: Our data indicated that the carrier rate of the p.D47E mutation of CBS gene in the Taitung area was only 1 out of 3,357, which indicated a low prevalence in Taiwan. As a result, it is our opinion that including point-mutation genetic assay for homocysteine is unnecessary for the screening newborns in Taiwan.